INHIBITION OF SYMPATHETIC NEUROTRANSMISSION BY THE OPIOID δ‐RECEPTOR AGONIST DAMA IN THE PITHED RAT

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Abstract
1. The effects of [d-Ala2, Met5]enkephalinamide (DAMA), an analogue of [Met5]-enkephalin that acts selectively on opioid receptors of the 8-subtype, were studied on pressor responses elicited by sympathetic stimulation in pithed rats. 2. Intravenous injections of bolus doses of 0.1 mg/kg and 0.3 mg/kg of DAMA did not affect either the basal blood pressure or pressor responses to noradrenaline. 3. Pressor responses elicited either by electrical stimulation of the spinal sympathetic outflow or by stimulation of sympathetic ganglion cells with the muscarinic agonist McN-A-343 were reduced by DAMA. 4. Naloxone (1 mg/kg + 0.5 mg/kg per h) had no significant effect on the basal blood pressure or on pressor responses to spinal sympathetic stimulation, but antagonised the inhibitory effect of DAMA. 5. These results indicate that activation of opioid 8-receptors on sympathetic vasomotor nerve terminals can inhibit noradrenergic neurotransmission.